Ifimol

Ifimol

paracetamol

Manufacturer:

Unique Pharma Lab

Distributor:

Unimed
Full Prescribing Info
Contents
Paracetamol.
Description
FC tablet: Each film coated tablets contains: Paracetamol 500 mg, Sodium Methyl Hydroxybenzoate 1 mg (As preservative).
Infusion soln: Each ml contains: Paracetamol 10mg, Water for Injection q.s.
Action
Infusion soln: Pharmacotherapeutic Group: OTHER ANALGESICS AND ANTIPYRETICS. ATC Code: N02BE01.
Pharmacology: FC tablet: Paracetamol may act by inhibiting prostaglandin synthesis in the CNS and through a peripheral action by blocking pain-impulse generation. The peripheral action may also be due to inhibition of the synthesis of prostaglandin or to inhibit the synthesis or action of other substances, which sensitize pain receptors to mechanical or chemical stimulation. Paracetamol probably produces antipyresis by acting centrally on the hypothalamic heat-regulating center to produce peripheral vasodilation resulting in increased blood flow through the skin, sweating and heat loss. The central action probably involves inhibition of prostaglandin synthesis in the hypothalamus.
Pharmacodynamics: Infusion soln: The precise mechanism of the analgesic and antipyretic properties of paracetamol has yet to be established; it may involve central and peripheral actions.
IFIMOL IV provides onset of pain relief within 5 to 10 minutes after the start of administration. The peak analgesic effect is obtained in 1 hour and the duration of this effect is usually 4 to 6 hours.
IFIMOL IV reduces fever within 30 minutes after the start of administration with a duration of the antipyretic effect of at least 6 hours.
Pharmacokinetics: FC tablet: Paracetamol is rapidly and completely absorbed from the gastrointestinal tract.
Approximately 85% of a 1 g dose is recovered from the urine in 24 hours, about 3% is excreted unchanged, the balance being conjugated principally to the glucuronide or sulfate. Peak plasma concentrations of the free and conjugated drug are achieved ½ to 1 Hour after administration. The plasma half life of the unchanged drug is about 2 hours.
Infusion soln: Adults: Absorption: Paracetamol pharmacokinetics is linear up to 2 g after single administration and after repeated administration during 24 hours.
The bioavailability of paracetamol following infusion of 500 mg and 1 g of IFIMOL IV is similar to that observed following infusion of 1 g and 2 g propacetamol (corresponding to 500 mg and 1 g paracetamol respectively). The maximal plasma concentration (Cmax) of paracetamol observed at the end of 15-minutes intravenous infusion of 500 mg and 1 g of IFIMOL IV is about 15 μg/ml and 30 μg/ml respectively.
Distribution: The volume of distribution of paracetamol is approximately 1 L/kg.
Paracetamol is not extensively bound to plasma proteins.
Following infusion of 1 g paracetamol, significant concentrations of paracetamol (about 1.5 μg/ml) were observed in the Cerebro Spinal Fluid as and from the 20th minute following infusion.
Metabolism: Paracetamol is metabolised mainly in the liver following two major hepatic pathways: glucuronic acid conjugation and sulphuric acid conjugation. The latter route is rapidly saturable at doses that exceed the therapeutic doses. A small fraction (less than 4%) is metabolised by cytochrome P450 to a reactive intermediate (N·acetyl benzoquinone imine) which, under normal conditions of use, is rapidly detoxified by reduced glutathione and eliminated in the urine after conjugation with cysteine and mercapturic acid. However, during massive overdosing, the quantity of this toxic metabolite is increased.
Elimination: The metabolites of paracetamol are mainly excreted in the urine. 90% of the dose administered is excreted in 24 hours, mainly as glucuronide (60-80%) and sulphate (20-30%) conjugates. Less than 5% is eliminated unchanged. Plasma half-life is 2.7 hours and total body clearance is 18 L/h.
Neonates, infants and children: The pharmacokinetic parameters of paracetamol observed in infants and children are similar to those observed in adults, except for the plasma half-life that is slightly shorter (1.5 to 2 h) than in adults. In neonates, the plasma half-life Is longer than in infants i.e. around 3.5 hours. Neonates, infants and children up to 10 years excrete significantly less glucuronide and more sulphate conjugates than adults.
Table 1. Age related pharmacokinetic values (standardized clearance, *CLstd/Foral (l.h-1 70kg-1), are presented as follows. (See Table 1.)

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Special populations: Renal Insufficiency: In cases of severe renal impairment (creatinine clearance 10-30 mL/min), the elimination of paracetamol is slightly delayed, the elimination half-life ranging from 2 to 5.3 hours.
For the glucuronide and sulphate conjugates, the elimination rate is 3 times slower in subjects with severe renal impairment than in healthy subjects. Therefore, it is recommended, when giving paracetamol to patients with severe renal impairment (creatinine clearance ≤30 mL/min), to increase the minimum interval between each administration to 6 hours (see Dosage & Administration).
Elderly subjects: The pharmacokinetics and the metabolism of paracetamol are not modified in elderly subjects. No dose adjustment is required in this population.
Indications/Uses
FC tablet: The treatment of mild to moderate pain and the reduction of fever.
Infusion soln: Paracetamol is indicated for the short-term treatment of moderate pain, especially following surgery, and for the short-term treatment of fever, when administration by intravenous route is clinically justified by an urgent need to treat pain or hyperthermia and/or when other routes of administration are not possible.
Dosage/Direction for Use
FC tablet: Adults and children over 10 years: 325 to 650 mg 4 to 6 times daily as necessary.
Children: The following amounts, or 175 mg/m2 of body surface, administered 4 times daily; under 1 year, 15 to 60 mg; 1 to 3 years; 60 to 120 mg; 3 to 6 years; 120 mg; 6 to 12 years; 150 to 300 mg. (Do not exceed more than 8 tablets in a day unless directed by the physician.)
Infusion soln: Intravenous route.
Posology: Dosing based on patient weight (see the dosing table as follows): (See Table 2.)

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The minimum interval between each administration must be at least 4 hours.
The minimum interval between each administration in patients with severe renal insufficiency must be at least 6 hours.
No more than 4 doses to be given in 24 hours.
Severe renal insufficiency: It is recommended, when giving paracetamol to patients with severe renal impairment (creatinine clearance ≤30 mL/min), to increase the minimum interval between each administration to 6 hours (see Pharmacology: Pharmacokinetics under Actions).
In adults with hepatocellular insufficiency, chronic alcoholism, chronic malnutrition (low reserves of hepatic glutathione), dehydration: The maximum daily dose must not exceed 3g (see Warnings and Precautions).
Method of administration: Parenteral.
Take care when prescribing and administering IFIMOL IV to avoid dosing errors due to confusion between milligram (mg) and milliliter (mL), which could result in accidental overdose and death. Take care to ensure the proper dose is communicated and dispensed.
When writing prescriptions, include both the total dose in mg and the total dose in volume. Take care to ensure the dose is measured and administered accurately.
Do not remove inner container from overwrap until ready for use.
The overwrap is a moisture barrier. The inner container maintains the sterility of the product.
After removing overwrap, check for minute leaks by squeezing the container. Do not use if leaks are found and return for replacement.
Bring the injection bottle to room temperature or preferably to 37°C just before use.
Clean the spout of injection bottle with surgical spirit.
Keep the bottle on a hard surface and insert the cannula of the sterile infusion set into the spout of injection bottle. (Note that the cannula of the infusion set should be inserted fully and not halfway into the spout of the Ifimol IV bottle to avoid leakage.)
For administration hang the bottle upside down.
Inject Intravenously slowly at a rate of about 5 mL/minute.
To admit air, insert a sterile injection cannula on the top of the inverted bottle anywhere above the level of the liquid.
Caution: Even inviable damage to bottle caused during storage or transit, may result in contamination. Do not use if leak found on squeezing, or contents not clear, and return for replacement.
Overdosage
FC tablet: Signs of overdose may appear shortly after ingestion ie., diarrhoea, vomiting or nausea, loss of appetite, stomach cramps or pain, unusual increase sweating.
If any over dosage is suspected seek medical assistance.
Infusion soln: There is a risk of liver injury (including fulminant hepatitis, hepatic failure, cholestatic hepatitis, cytolytic hepatitis), particularly in elderly subjects, in young children, in patients with liver disease, in cases of chronic alcoholism, in patients with chronic malnutrition and in patients receiving enzyme inducers. Overdosing may be fatal in these cases.
Symptoms generally within the first 24 hours and comprise: nausea, vomiting, anorexia, pallor, abdominal pain. Overdose, 7.5 g or more of paracetamol in a single administration in adults and 140 mg/kg of body weight in a single administration in children, causes hepatic cytolysis likely to induce complete and irreversible necrosis, resulting in hepatocellular insufficiency, metabolic acidosis and encephalopathy which may lead to coma and death.
Simultaneously, increased levels of hepatic transaminases (AST, ALT), lactate dehydrogenase and bilirubin are observed together with decreased prothrombin levels that may appear 12 to 48 hours after administration.
Clinical symptoms of liver damage are usually evident initially after two days, and reach a maximum after 4 to 6 days.
Emergency measures: Immediate hospitalisation.
Before beginning treatment, take a tube of blood for plasma paracetamol assay, as soon as possible after the overdose.
The treatment includes administration of the antidote, N-acetylcysteine (NAC), by the i.v. or oral route, if possible before the 10th hour. NAC can, however, give some degree protection even after 10 hours, but in these cases prolonged treatment is given.
Symptomatic treatment.
Hepatic tests must be carried out at the beginning of treatment and repeated every 24 hours. In most cases hepatic transaminases return to normal in one to two weeks with full restitution of liver function. In very rare cases, however, liver transplantation may be necessary.
Contraindications
FC tablet: Hypersensitivity to paracetamol.
Injection soln: IFIMOL IV is contraindicated: in patients with hypersensitivity to paracetamol or to propacetamol hydrochloride (prodrug of paracetamol) or to one of the excipients; in cases of severe hepatocellular insufficiency.
Warnings
Infusion soln: RISK OF MEDICATION ERRORS: Take care to avoid dosing errors due to confusion between milligram (mg) and milliliter (mL), which could result in accidental overdose and death (see Dosage & Administration).
This preparation contains PARACETAMOL.
Do not take any other paracetamol containing medicine at the same time.
Allergy alert: Paracetamol may cause severe skin reactions. Symptoms may include skin reddening, blisters or rash. These could be sign of a serious condition. If these reactions occur, stop use seek medical assistance right away.
This preparation contains Sodium metabisulphite that may cause serious allergic type reactions in certain susceptible patients. Do not use of known to be hypersensitive to bisulphites.
Special Precautions
FC tablet: When used correctly, paracetamol is safe to take paracetamol should be used with caution in patients who are renally or hepatically impaired, depended on alcohol or malnourished. This product contains paracetamol. Do not take any other products containing paracetamol at the same time. Allergy alert: Paracetamol may cause severe skin reactions. Symptoms may include skin reddening, blisters or rash. These could be signs of a serious condition. If these reactions occur, stop use seek medical assistance right away.
Infusion soln: It is recommended that a suitable analgesic oral treatment be used as soon as this route of administration is possible.
In order to avoid the risk of overdose, check that other medicines administered do not contain either paracetamol or propacetamol.
Doses higher than those recommended entail the risk of very serious liver damage.
Clinical signs and symptoms of liver damage are not usually seen until two days, and up to a maximum of 4-6 days, after administration. Treatment with antidote should be given as soon as possible (see Symptoms and Treatment of Overdose under Overdosage).
Precautions for use: Paracetamol should be used with caution in cases of: hepatocellular insufficiency, severe renal insufficiency (creatinine clearance <30mL/min), chronic alcoholism, chronic malnutrition (low reserves of hepatic glutathione), dehdydration.
Effects on Ability to Drive and Use Machines: It is unlikely to impair a patient's ability to drive or use machinery.
Use In Pregnancy & Lactation
Infusion soln: Pregnancy: Clinical experience of intravenous administration of paracetamol is limited. However, epidemiological data from the use of oral therapeutic doses of paracetamol indicate no undesirable effects on the pregnancy or on the health of the foetus / newborn infant.
Prospective data on pregnancies exposed to overdoses did not show an increase in malformation risk.
Reproductive studies with the intravenous form of paracetamol have not been performed in animals. However, studies with the oral route did not show any malformation of foetotoxic effects.
Nevertheless, IFIMOL IV should only be used during pregnancy after a careful benefit risk assessment. In this case, the recommended posology and duration must be strictly observed.
Lactation: After oral administration, paracetamol is excreted into breast milk in small quantities. No undesirable effect on nursing infants have been reported. Consequently, IFIMOL IV may be used in breast-feeding women.
Side Effects
FC tablet: Incidence of side effects are rare, but if any of the following symptom occur consult the physician immediately.
Bloody of cloudy urine, difficult or painful urination, frequent urge to urinate, sudden decrease amount of urine, skin rashes, hives or itching unusual bleeding or bruising, unusual tiredness or weakness, yellowing of eyes or skin.
Cutaneous hypersensitivity reactions including skin rashes, angioedema, Stevens Johnson Syndrome/Toxic Epidermal Necrolysis have been reported.
Infusion soln: As all paracetamol products, adverse drug reactions are rare (>1/10000, <1/1000) or very rare (<1/10000), they are described as follows: (See Table 3.)

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Frequent adverse reactions at injection site have been reported during clinical trials (pain and burning sensation).
Very rare cases of hypersensitivity reactions ranging from simple skin rash or urticaria to anaphylactic shock have been reported and require discontinuation of treatment.
Cases of erythema, flushing, pruritus and tachycardia have been reported.
Cutaneous hypersensitivity reactions including skin rashes, angioedema, Stevens Johnson Syndrome/Toxic Epidermal Necrolysis have been reported.
Drug Interactions
FC tablet: It is possible that paracetamol may react with warfarin with prolonged, regular use.
Infusion soln: Probenecid causes an almost 2-fold reduction in clearance of paracetamol by inhibiting its conjugation with glucuronic acid. A reduction of the paracetamol dose should be considered for concomitant treatment with probenecid, Salicylamide may prolong the elimination t½ of paracetamol,
Caution should be paid to the concomitant intake of enzyme-inducing substances (see Symptoms and Treatment of Overdose under Overdosage).
Concomitant use of paracetamol (4 g per day for at least 4 days) with oral anticoagulants may lead to slight variations of INR values. In this case, increased monitoring of INR values should be conducted during the period of concomitant use as well as for 1 week after paracetamol treatment has been discontinued.
Caution For Usage
Infusion soln: Special precautions for disposal and other handling: Text for the 100ml bottle: Use a 0.8 mm needle and vertically perforate the stopper at the spot specifically indicated.
Before administration, the product should be visually inspected for any particulate matter and discoloration. For single use only. Any unused solution should be discarded.
The diluted solution should be visually inspected and should not be used in presence of opalescence, visible particulate matters or precipitate.
Incompatibilities: IFIMOL IV should not be mixed with other medicinal products.
Storage
Store below 30°C.
FC tablet: Protect from light.
Shelf-Life: FC tablet: 5 Years.
Infusion soln: 24 months.
ATC Classification
N02BE01 - paracetamol ; Belongs to the class of anilide preparations. Used to relieve pain and fever.
Presentation/Packing
FC tab 500 mg (pink coloured capsules shaped) x 10 x 10's, 100 x 10's. Infusion soln 10 mg/mL (a clear colorless sterile solution) x 100 mL.
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